A basic problem in the construction of medical devices having components that must contact blood and other physiological fluids is that materials with good mechanical and structural properties have rather poor biocompatibility, while highly biocompatible materials have poor structural properties. Biocompatibility is itself a multi-faceted problem which has different aspects depending on the type of device, what tissues or fluids it contacts, and the length of contact time. In devices designed for hemodialysis or blood oxygenation, the materials are in contact with blood flowing through tubing, into containers, and over membranes. The blood returns to the patient's body. The primary elements of biocompatibility are therefore to prevent initiating processes which can subsequently injure the patient, such as activation of clotting mechanisms, activation of the complement system, and initiation of inflammatory reactions. Materials must not be soluble in blood or other body fluids to avoid being carried permanently into the patient's body.
Although certain types of polymers, such as silicones and siloxanes, are known to possess many attributes of biocompatibility, there are no reliable physical correlates which enable one to predict biocompatibility with any degree of certainty. Generally, hydrophobic surfaces are more biocompatible than hydrophilic surfaces. Zisman's critical surface tension Zisman, W. A. (1964) Adv. Chem. Ser. 43! has been used as a parameter to help assess potential biocompatibility. Materials with an optimum critical surface tension are frequently biocompatible, yet there are notable exceptions. For example, polyethylene and polypropylene have critical surface tensions well within the optimum range, but they are not biocompatible. Other factors are also important. Without a clear understanding of the nature of these factors, biocompatibility remains unpredictable.
Because of the attractive structural properties of polyolefins and polyurethanes, various blending and co-polymerization techniques have been developed to impart greater biocompatibility. U.S. Pat. No. 4,872,867 discloses modifying a polyurethane with a water soluble polymer and crosslinking them in situ with a silane type coupling agent to form a cross-linked and intertwined polysiloxane network. U.S. Pat. No. 4,636,552 discloses a polydimethyl siloxane with polylactone side chains which are said to be useful for imparting biocompatibility when combined with a base polymer, or used to replace plasticizer. U.S. Pat. No. 4,929,510 discloses a diblock copolymer having a more hydrophobic block and a less hydrophobic block. A solution of the diblock copolymer in a solvent which swells the matrix polymer is used to introduce the diblock into an article of matrix polymer. Thereafter, the article is transferred to water, to force orientation of the incorporated diblock copolymer such that the more hydrophobic block is embedded in the matrix and the less hydrophobic block is exposed on the surface of the article. Examples of diblock copolymers included poly (ethyleneoxide-propylene oxide), N-vinyl-pyrrolidone-vinyl acetate and N-vinyl-pyrrolidone-styrene. U.S. Pat. Nos. 4,663,413 and 4,675,361 disclose segmented block copolymers, in particular polysiloxane-polycaprolactone linear block copolymers. The latter were incorporated into base polymer materials to modify the surface properties thereof. Although initially blended in bulk into the base polymer, the copolymer migrates to the surface to form an exceptionally thin, possibly a monolayer film which imparts the desired surface characteristic, specifically, biocompatibility.
U.S. Pat. No. 4,963,595 discloses block copolymers having polycaprolactone blocks and polysiloxane blocks useful as additives to modify a base polymer, such as nylon, and to modify the surface properties thereof. Triblock copolymers having a polysiloxane block flanked by polycaprolactone blocks are commercially available, for example from Thoratec Laboratories, Berkeley, Calif. The abbreviation LSL is used herein to designate triblock copolymers of polylactone-polydimethylsiloxane-polylactone type, generally, and the abbreviation PDMS is used to designate the polydimethylsiloxane block, generally. Thoratec Laboratories provides a series of such polymers designated "SMA" in which the siloxane is dimethyl siloxane and the lactone is caprolactone. The nominal molecular weights (number average) of the polysiloxane blocks suitable for use herein range from about 1000 to about 5000, while the nominal molecular weights of the caprolactone blocks range from about 1000 to about 10,000. A LSL triblock copolymer having polycaprolactone blocks of 1000 and polysiloxane blocks of 1000 (SMA-411) has been shown to be usable, as has a copolymer having polycaprolactone blocks of 10,000 and polysiloxane blocks of 5000 (SMA-4-10-5).
U.S. Pat. No. 3,686,355 disclosed that surface properties of wettability and surface friction could be reduced by addition of block copolymer additives of bisphenol-A and polydimethylsiloxane. It was noted that the effective concentration of the surface-active block copolymer additive at the surface of a shaped polymer composition appeared to depend on the nature of the substrate against which the shaping was carried out, for example by solvent casting or molding. It was believed that a high energy surface substrate material such as glass, mica, metals or metal oxides, adsorbed the copolymer additive from the base polymer surface in contact with it, resulting in loss of copolymer from the polymer surface after separation from the substrate surface. The surface effects of decreased wettability and friction provided by addition of the copolymer additive were therefore maximized by annealing the shaped article or by a solvent application to soften the surface to allow copolymer additive to pass to the surface of the article.
LeGrand et al, (1970) Am. Chem. Soc., Div. Polymer Chem. Preprints 11:442-446, reported studies using bisphenol-A polycarbonate base polymer mixed with an added alternating block copolymer of bisphenol-A carbonate and polydimethylsiloxane (PDMS), measuring ethylene glycol contact angles and static friction coefficients to assess surface hydrophobicity presumably related to surface concentration of the additive. Contact angle on a sample having 1% additive was greater on sample molded between teflon-coated foils than on sample molded between mica sheets.
Polycarbonate is a very useful base polymer for medical devices intended for blood contact, for example blood oxygenators, heat exchangers and dialyzers used in heart surgery, transplant surgery, kidney dialysis and the like. Polycarbonate is advantageous for such applications for a variety of reasons, notably for purposes of the invention herein, because it can be fabricated by molding to achieve complex shapes, and because the devices made of polycarbonate are essentially transparent. The latter is an important consideration for medical personnel using the devices, permitting them to see at a glance whether blood is flowing properly. LSL triblock copolymers are attractive candidates for bulk additives to improve the biocompatibility of polycarbonate surfaces. A problem is encountered when a polycarbonate base polymer is molded with an LSL copolymer. At concentrations greater than about 0.2% of LSL copolymer by weight, optical clarity of the blended material is degraded or lost, the blend becoming cloudy or opaque, possibly due to phase separation of the LSL copolymer. In consequence, the benefits of improved biocompatibility by the addition of an LSL copolymer are compromised by the loss of transparency when sufficient LSL is incorporated to provide adequate biocompatibility.